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Hiroshi Inoue

Publications and source records attributed to Hiroshi Inoue.

At least 109 records · Page 6Linked to original sources
PubMed2005

[A case of interval form of carbon monoxide poisoning with a remarkable recovery].

A 69-year-old woman was admitted to our hospital due to an interval form of carbon monoxide (CO) poisoning one month after acute CO poisoning. On admission, she had disorientation, memory disturbance, apathy, masked face, muscle rigidity, bradykinesia and parkisonian gait. An MRI (FLAIR image) revealed high signal intensity lesions in the bilateral globus pallidus and the white matter of the frontal lobe. Hyperbaric oxygen (HBO) therapy at 2 atmospheres for 60 min was given every day, in addition to citicoline, levodopa/DCI and selegiline hydrochloride. Cognitive disturbance and parkinsonism gradually decreased, and abnormal signals in the bilateral globus pallidus and the cerebral white matter were attenuated after the treatment. Neuropsychiatric abnormalities except for a slight gait disturbance disappeared one and a half month after starting the treatment. In addition to HBO therapy, administration of citicoline, lovodopa and selegiline may be useful in the case of the interval form of CO poisoning.

Acute Disease↗
PubMed2005

Cell binding isoforms of vascular endothelial growth factor-A (VEGF189) contribute to blood flow-distant metastasis of pulmonary adenocarcinoma.

Vascular endothelial growth factor A (VEGF-A) has two kinds of isoforms depending on cellular binding domains. VEGF189 is the largest molecule with the strongest cellular binding ability, and is thought to be most potent for vascularization in various cancers. This study aims to clear the clinicopathological characteristics of VEGF189 in the pulmonary adenocarcinoma. We finely and quantitatively examined the expression of VEGF-A isoforms (VEGF121, VEGF165 and VEGF189) by real-time polymerase chain reaction in a total of 100 pulmonary adenocarcinomas resected by surgical operation. The VEGF isoform expression status was analyzed on clinicopathological features including stromal vascularization, vascular involvement, distant metastasis, lymph nodal metastasis, postoperative relapse time and prognosis of long-term observation periods. All the pulmonary adenocarcinomas showed significant expression of VEGF-A. Twenty-two cases with the adenocarcinomas overexpressing VEGF-A significantly showed earlier postoperative relapse and poorer prognosis between 5- to 15-year periods (p = 0.0093 and p = 0.0240, Kaplan Meier, log-rank test). The expression levels of VEGF189 increased in 13% of the pulmonary adenocarcinoma. These 13 cases with increased VEGF189 expression significantly showed higher distant metastases, earlier postoperative relapse, and poorer prognosis (p = 0.0006, Fisher's test; p = 0.0016 and p = 0.0084, Kaplan Meier, log-rank test) than the other 87 cases. The 13 lung cancers with VEGF189 overexpression also showed increased vessel counts, areas (p = 0.0091 and p < 0.0001, Mann-Whitney U test) and enhanced venous involvement (p = 0.0056, Fisher's test). The cellular binding isoform VEGF189 confers pulmonary adenocarcinoma patients with poorer prognosis with distant metastasis via blood flow.

Adenocarcinoma↗
PubMed2005

The high expression of Fractalkine results in a better prognosis for colorectal cancer patients.

Local and systemic immune responses are impaired in patients with colorectal cancer (CRC) and it is known that the number of tumor infiltrating lymphocytes (TILs) is considerably few. On the other hand, some CRC cases in which many TIL were observed, survived longer than those cases with a small number of TIL. Considerable attention has been recently paid to the relationship between chemokines and tumor cells. Some chemokines recruit lymphocytes for tumor lesions. We made a hypothesis that Fractalkine, a CX3C chemokine, would recruit lymphocytes in the CRC and play an important role in anti-tumor immunity. We analyzed the expression level of Fractalkine in CRC cell lines as well as in clinical samples (n=80). The expression level of Fractalkine was thus found to correlate with the density of TIL (p<0.05). The CRC cases with a strong Fractalkine expression (n=50) showed a significantly better prognosis than those with a weak expression (n=30) (p<0.05). In addition, the Fractalkine expression was found to be an independent prognostic factor (p<0.05). We furthermore clarified that some of the tumor-infiltrating cells were natural killer cells and cytotoxic T cells expressed Fractalkine receptor. These data suggest that Fractalkine expressed in the tumor appears to recruit cytotoxic T cells and NK cells to the tumor site and these cytotoxic cells result in a better prognosis mediated by tumor cell cytotoxicity using a perforin and granzyme B mechanism. The expression level of Fractalkine was an essential biomarker for predicting the prognosis of patients with CRC. Fractalkine is considered to be one of the biomarkers for detecting patients with a high risk for recurrence, and who might therefore benefit from additional therapeutic strategies such as adjuvant therapy.

Biomarkers, Tumor↗
PubMed2005

Evaluation of fatty acid metabolism in hearts after ischemia-reperfusion injury using a dual-isotope autoradiographic approach and tissue assay for metabolites of tracer.

UNLABELLED: We investigated whether changes in myocardial uptake of fatty acid tracer after reperfusion following transient myocardial ischemia were closely related to alterations in intracellular fatty acid oxidation. METHODS: Using a fatty acid tracer of (131)I- and (125)I-labeled 15-(p-iodophenyl)-9-methylpentadecanoic acid (9MPA), the myocardial uptake and metabolites were determined by dual-tracer autoradiography and thin-layer chromatography in rats 3 or 14 d after reperfusion following 5 or 15 min of ischemia induced by coronary artery ligation. RESULTS: 9MPA metabolites processed via beta-oxidation were lower in the ischemic region (IR) than in non-IR 3 d after 5 min of ischemia, despite no reduction of tracer uptake in IR. Oxidation of 9MPA was recovered 14 d after 15 min of ischemia in association with normalization of tracer uptake in IR, whereas both uptake and oxidation of 9MPA were markedly impaired 3 d after 15 min of ischemia, accompanied by slow clearance of myocardial tracer. CONCLUSION: Normal uptake of fatty acid tracer early after reperfusion does not always imply preserved intracellular fatty acid oxidation. However, reduction of tracer uptake might reflect impaired fatty acid oxidation.

Animals↗
PubMed2005

Detection of occult cancer cells in peripheral blood and bone marrow by quantitative RT-PCR assay for cytokeratin-7 in breast cancer patients.

The clinical significance of occult micrometastasis (O.M) remains unknown. We investigated it in peripheral blood (P.B.) and bone marrow (B.M.) in breast cancer patients with surgery. First, we investigated the expression levels of 7 representative molecular markers for detecting O.M (CEA, CK-7, CK-18, CK-19, CK-20, MAM and MUC-1) in 27 cancer and 8 non-epithelial cell lines using quantitative RT-PCR (QRT-PCR), and showed that the expression level of CK-7 was higher in every cancer cell line than in the non-epithelial cell lines. Next, we studied the clinical significance of O.M in P.B. and B.M. by QRT-PCR for CK-7 in breast cancer patients with surgery. Based on comparison with 17 non-cancer controls, 37 (18.0%) and 100 (48.5%) of the 206 patients were positive for CK-7 in P.B. and B.M., respectively. In 98 cases observed over 24 months after surgery, the CK-7-positive group in P.B. had poorer disease-free survival (DFS) than the negative group (p<0.01). The CK-7-positive group in P.B. showed poorer DFS than the negative group in 132 lymph node-negative cases (p=0.01), and moreover, in 61 lymph node-negative cases observed over 24 months after surgery, the CK-7-positive group in P.B. showed poorer DFS than the negative group (p<0.0001). In B.M., no significant difference in DFS was found between the CK-7-positive and CK-7-negative groups. QRT-PCR for CK-7 could be a useful and universal method for detecting O.M, and the quantitative detection of CK-7 in P.B. would have a prognostic value as a marker of early recurrence in breast cancer patients with surgery.

Adult↗
PubMed2005

Aberrant expression of the gastric mucin MUC6 in human pulmonary adenocarcinoma xenografts.

Certain pulmonary adenocarcinomas show gastrointestinal differentiation with the expression of various mucins. The CDX homeobox gene, an intestine-specific transcription factor, is related to gastric carcinogenesis with MUC2 and MUC6 expression. The intestinal mucin MUC2 is expressed in the normal lung, while the gastric mucin MUC6 is not. Previously, we have reported that the expressions of MUC2 and MUC6 were related to a poor prognosis in small adenocarcinomas of the lung. We estimated the expressions of the mucin (MUC2 and MUC6) and CDX (CDX1 and CDX2) to examine how CDX relates to the gastrointestinal mucin production in the pulmonary adenocarcinoma. Thirty-nine human non-small cell lung cancer (NSCLC) xenografts were examined (13 adenocarcinoma, 18 squamous cell carcinoma and 8 large cell carcinoma). Significant expression of the MUC6 gene was observed in 7 out of 39 (17.9%) NSCLC xenografts. The expressions of the MUC6 genes were noted in 6 out of 13 (46.2%) adenocarcinoma xenografts, but only in 1 of 18 (0.06%) squamous cell carcinoma xenografts. The adenocarcinoma xenografts significantly showed higher expression of the MUC6 gene than squamous cell carcinoma xenografts (t-test, p=0.0343). Four adenocarcinoma-xenografts co-expressed both the MUC2 and MUC6 genes, and the residual 2 adenocarcinoma-xenografts expressed only the MUC6 gene. One MUC6 overexpressing squamous cell carcinoma focally contained an adenocarcinoma component. The expression patterns of the gastrointestinal mucins were analogous to gastric cancer. The cellular morphology of these carcinoma xenografts was of the gastric cancer type. The proteins of the MUC2 and MUC6 were immunohistochemically confirmed in the xenografts. The expression of the MUC6 gene was significantly correlated with the expressions of the CDX1 and CDX2 genes in the xenografts (Fisher's test, p<0.0001 and p=0.0005, respectively), while there was no significant association between the expression of the MUC2 and CDX genes. These results suggest that the expression of CDX molecules in the pulmonary carcinogenesis pathway relates to gastric cancerous features of aberrant MUC6 expression.

Adenocarcinoma↗
PubMed2005

[Arrhythmias].

There are several underlying factors including anatomical substrates (coronary artery disease, cardiomyopathy, valvular disease, congenital heart disease, WPW syndrome) and modulating factors(autonomic nervous system, electrolyte balance, drugs) which may induce sudden cardiac death. Although studies evaluating mechanisms of sudden cardiac death are increasing, evaluation of risk of each patient and effectiveness of preventive treatments are still inadequate. Sudden death due to life threatening arrhythmias in the out-of-hospital situation can be resuscitated by non-medical staff with automated external defibrillator. In these resuscitated high-risk patients implantable cardioverter and defibrillator could be used to prevent sudden death due to unpreventable further arrhythmic episodes. Widespread availability of automated external defibrillator is mandatory.

Arrhythmias, Cardiac↗
PubMed2005

Genomic screens for genes upregulated by demethylation in colorectal cancer: possible usefulness for clinical application.

Inactivation of tumor suppressor genes may result in clinically aggressive tumors and poor prognoses for cancer patients. This study was conducted to investigate the clinical significance of genomic screens for genes upregulated by demethylation in colorectal cancer. We performed a comprehensive survey of commonly inactivated genes in colorectal cancer through the functional reactivation of epigenetically silenced genes by 5-Azacytidine, using cDNA microarrays containing 12,814 genes. We then investigated the clinical significance of the identified gene in colorectal cancer patients. Among 41 candidate genes identified by this microarray analysis, 31 (76%) harbored CpG islands, and many of the genes were associated with cancer-testis antigens, Wnt inhibitors, growth factors, and cell cycle regulators. Subsequent analysis by quantitative RT-PCR confirmed the reliability of our microarray strategy. In order to elucidate the potential clinical significance of these identified genes, we selected one of these genes, apolipoprotein D (apo D), and investigated its mRNA expression in 63 colorectal cancer patients using quantitative real-time RT-PCR. The mean expression level of Apo D mRNA was significantly lower in cancerous tissues than in non-cancerous tissues (p < 0.01), and a lower expression of Apo D was significantly correlated with lymph node metastasis (p < 0.05), advanced stages (p < 0.05) and poorer overall survival (p < 0.05). These results indicated that a genomic screen for genes upregulated by demethylation may be a useful approach for the identification of genes that are of clinical significance in colorectal cancer patients.

Aged↗
PubMed2005

Genetic susceptibility of catechol-O-methyltransferase polymorphism in Japanese patients with breast cancer.

Polymorphic catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens. It has been reported that COMT polymorphism is a representative genetic trait related to the susceptibility of an individual to breast cancer. However, there is no consensus concerning the association between breast cancer in Japanese patients and COMT polymorphism. To analyze the polymorphism distribution in Japanese patients with breast cancer, a molecular genotyping method using a polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was used. Based on an analysis of 201 Japanese patients with breast cancer and 352 healthy control subjects, a significant difference was observed in either the distribution of genotypes (p=0.03) or allele frequencies between the two groups (p=0.01). The relative risk of breast cancer for genotypes (COMT(Met/Met) and COMT(Val/Met)) including the variant allele (COMT(Met)) was 1.47 compared to the wild allele (COMT(Val)) and homozygote (COMT(Val/Val)). Furthermore, the distribution of genotypes in post-menopausal patients with breast cancer showed a significant difference with that of healthy subjects of the same menopausal status (p=0.01). No significant difference was found between the distribution of genotypes and clinicopathological features of the cancer. These results suggest that COMT polymorphism may thus be implicated as a genetic trait affecting the susceptibility of an individual to breast cancer in a Japanese population and be an important genetic risk factor in the development of breast cancer in post-menopausal women.

Adult↗
PubMed2005

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2003)].

From October 2003 to September 2004, we collected the specimen from 399 patients with lower respiratory tract infections in 12 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 474 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 469 strains were examined. The breakdown of the isolated bacteria were: Staphylococcus aureus 76, Streptococcus pneumoniae 81, Haemophilus influenzae 84, Pseudomonas aeruginosa (non-mucoid) 56, P. aeruginosa (mucoid) 11, Klebsiella pneumoniae 36, Moraxella subgenus Branhamella catarrhalis 24, etc. Of 76 S. aureus strains, those with 2 microg/ml or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 microg/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were both 38 strains (50.0%). Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all the strains at 0.063 microg/mL. Against MRSA, vancomycin showed the most potent activity and inhibited the growth of all the strains at 2 microg/mL. Arbekacin also showed the potent activity and inhibited the growth of all the strains at 4 microg/mL. Carbapenems showed the most potent activities against S. pneumoniae and inhibited the growth of all the strains at 0.125-0.5 microg/mL. Cefozopran (CZOP) also had a preferable activity (MIC90:2 microg/ mL) and inhibited the growth of all the strains at 4 microg/mL. In contrast, there were high-resistant strains (MIC: 128 microg/mL or more) for cefaclor (11.1%), erythromycin (43.2%), and clindamycin (40.7%). Against H. influenzae, levofloxacin showed the most potent activity and inhibited the growth of 83 of all the strains (98.8%) at 0.063 microg/mL. Tobramycin showed the most potent activity against P. aeruginosa (both mucoid and non-mucoid) and its MIC90 was 2 microg/mL. The activity of CZOP also was preferable and its MIC90 was 4 microg/mL for the mucoid-type and 8 microg/mL for the non-mucoid type. CZOP was the most potent activities against K. pneumoniae and inhibited the growth of all the strains at 0.125 microg/mL. Also, all the agents generally showed potent activities against M. (B.) catarrhalis and the MIC90 of them were 4 microg/mL or less. The approximately half the number (54.1%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 46.1% and 30.6% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (18.6%) and H. influenzae (18.1%). In contrast, S. aureus (16.9%) and S. pneumoniae (14.9%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (20.6%) and H. influenzae (21.5%). The bacteria relatively frequently isolated from the patients treated with cephems or macrolides were P. aeruginosa, and S. aureus was relatively frequently isolated from the patients treated with quinolones.

Aged↗
PubMed2005

Video-assisted thoracoscopic surgery under local anesthesia for right empyema secondary to aspiration pneumonia caused by esophageal achalasia: case report.

A 55-year-old man was admitted to the Department of Internal Medicine of our hospital with chief complaints of fever, cough, and right-sided chest pain. Plain radiography of the chest revealed widening of the mediastinum (attributed to esophageal achalasia), pneumonia, and right pleural effusion. According to the properties of the pleural fluid, empyema was diagnosed. Because the empyema was resistant to antibiotic treatment and was in the fibrinopurulent stage, it could not be drained effectively. Therefore, after treatment of the esophageal achalasia by balloon dilatation of the lower esophagus, the empyema was treated by video-assisted thoracoscopic surgery, i.e., by video-assisted thoracoscopic drainage and curettage of the empyema cavity, under local anesthesia.

Anesthesia, Local↗
PubMed2005

Knowledge of smoking-related risks and opinions on tobacco control by smoking status and education level in Japan.

OBJECTIVE: We aimed to examine knowledge of smoking-related risks and opinions on tobacco control by smoking status and education level in Japan. METHODS: We conducted a questionnaire survey in 2002 on a random sample of residents aged 20 to 79 years in two neighboring districts of northern Japan. In a total sample of 7,136, we analyzed data from 5,638 (79.0%) subjects (2,659 men and 2,979 women). RESULTS: The length of education was positively associated with knowledge of smoking-related risks. Compared to current smokers, past male smokers and never female smokers were more likely to know about the harm of passive smoking. As for causal links between smoking and lung cancer, stroke, and low birth weight, those who had been educated longer tended to be more aware of the associations in both sexes. Compared to current smokers, past and never smokers of men and past smokers of women were more likely to know that smoking contributes to low birth weight, but no difference was observed between current and never female smokers in this regard. Opinions on tobacco control were associated with both smoking status and education level; past and never smokers compared to current smokers and those who were educated longer tended to be affirmative about tobacco control. CONCLUSION: Knowledge of smoking is largely associated with education, but opinions on tobacco control are dependent on both smoking status and education.

Adult↗
PubMed2004

Coexpression of matrix metalloproteinase-7 (MMP-7) and epidermal growth factor (EGF) receptor in colorectal cancer: an EGF receptor tyrosine kinase inhibitor is effective against MMP-7-expressing cancer cells.

PURPOSE: Matrix metalloproteinase-7 (MMP-7) plays an important role in carcinoma invasion and metastasis of cancer. Recent studies focus on diverse roles of MMP-7, other than as a protease, during cancer progression. MMP-7 activates the epidermal growth factor (EGF) receptor by releasing an EGF ligand, tumor growth factor (TGF)-alpha. EXPERIMENTAL DESIGN: We examined expression of MMP-7 and EGF receptor in an immunohistochemical study of 40 colorectal cancer (CRC) cases. To determine the relationship between the EGF receptor and MMP-7, with a potential curative application, we compared the antitumor activity of the EGF receptor tyrosine kinase inhibitor (gefitinib) between MMP-7 transfectant, KYSE150 and HT29, and control cells. RESULTS: We found a statistically significant correlation (P = 0.04) between MMP-7 and activated (phosphorylated) EGF receptor expression, both being positive in six (15%) cases. Gefitinib reduced the cell number ratio more for MMP-7 transfectant than mock cells, and the proportion of apoptotic cells was 1.5 times higher in MMP-7 transfectant than mock cells by annexin/propidium iodide staining. This was mediated by activation of a TGF-beta signal as confirmed by the abundant expression of TGF-beta protein, the cytoplasmic to nuclear translocation of Smad4 protein by the administration of gefitinib, and the quantitative assay of the plasminogen activator inhibitor-1 promoter/luciferase construction. CONCLUSIONS: We propose that there are some cancers with up-regulated MMP-7 expression that leads to the activation of apoptotic activity of TGF-beta, which is susceptible to treatment with EGF receptor tyrosine kinase inhibitor.

Adult↗
PubMed2004

Studies of nonnucleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides.

A random high-throughput screening (HTS) program to discover novel nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been carried out with MT-4 cells against a nevirapine-resistant virus, HIV-1(IIIB-R). The primary hit, a thiazolidenebenzenesulfonamide derivative, possessed good activity. A systematic modification program examining various substituents at the 3-, 4-, and 5-positions on the thiazole ring afforded compounds with enhanced anti-HIV-1 and reverse transcriptase (RT) inhibitory activities. These results confirm the important role of the substituents at these positions and the thiazolidenebenzenesulfonamide motif as a valuable lead series for the next generation NNRTIs.

Benzenesulfonates↗
PubMed2004

Structural and functional analysis of pancreatic islets preserved by pioglitazone in db/db mice.

To evaluate preventive effects of pioglitazone on pancreatic beta-cell damage in C57BL/KsJ db/db mice, an obese diabetic animal model, the pancreatic islets were compared morphologically between pioglitazone-treated (100 mg/kg daily po) and untreated db/db mice (n = 7 for each) after a 12-wk intervention (6-18 wk of age). The fasting blood glucose level was significantly improved by the treatment with pioglitazone (260 +/- 12 vs. 554 +/- 62 mg/dl, P < 0.05). The islet mass in the pancreas was significantly greater in pioglitazone-treated mice than in untreated mice (10.2 +/- 1.1 vs. 4.6 +/- 0.2 mg, P < 0.01). Subsequently, biochemical and physiological analyses of the beta-cell function were employed using pioglitazone-treated and untreated db/db mice (n = 6 for each) and pioglitazone-treated and untreated db/+ mice (n = 6 for each). After 2 wk of treatment (10-12 wk of age), the plasma levels of triglyceride and free fatty acid were significantly decreased, whereas the plasma adiponectin level increased significantly compared with the untreated group (65.2 +/- 18.0 vs. 18.3 +/- 1.3 microg/ml, P < 0.05). Pioglitazone significantly reduced the triglyceride content in the islets (43.3 +/- 3.6 vs. 65.6 +/- 7.6 ng/islet, P < 0.05) with improved glucose-stimulated insulin secretion. Pioglitazone showed no significant effects on the biochemical and physiological parameters in db/+ mice. The present study first demonstrated that pioglitazone prevents beta-cell damage in an early stage of the disease progression in db/db mice morphologically and physiologically. Our results suggest that pioglitazone improves glucolipotoxicity by increasing insulin sensitivity and reducing fat accumulation in the pancreatic islets.

Adiponectin↗
PubMed2004

N-cadherin is regulated by activin A and associated with tumor aggressiveness in esophageal carcinoma.

PURPOSE: Activin A is a member of the transforming growth factor beta superfamily and plays an important role in the differentiation of embryonic stem cells. We have reported previously that the expression of activin A is associated with lymph node metastasis in esophageal cancer, and our purpose in the current work is to clarify the molecular mechanism of the aggressive behavior of tumors that have high activin A expression. EXPERIMENTAL DESIGN: We have compared the gene expression profiles of human esophageal carcinoma cell lines that were stably transfected with activin beta A, which is a subunit of activin A, with those of control human esophageal carcinoma cell lines, using a cDNA microarray. RESULTS: We found that the expression level of neuronal cadherin (N-cadherin) was higher in the transfectants than in the control cells. N-cadherin was located on the cell surface of the transfectants, irrespective of the expression of epithelial cadherin (E-cadherin), and the expression of N-cadherin mRNA was significantly associated with that of activin beta A mRNA in clinical samples of esophageal carcinoma (n = 51; r = 0.855). A clinicopathologic analysis suggested that expression of N-cadherin mRNA was associated with the depth of tumor wall invasion, and a group of patients with high expression of N-cadherin mRNA showed a significantly poorer prognosis than a group of patients with low N-cadherin expression (P = 0.046). CONCLUSIONS: These results indicate that activin A might mediate the expression of N-cadherin and that this may be associated with depth of invasion and poor prognosis.

Activins↗
PubMed2004

Differential expression of MMP and uPA systems and prognostic relevance of their expression in esophageal squamous cell carcinoma.

Matrix metalloproteinase (MMP) is critical for carcinoma progression. In our study, we evaluated the prognostic significance of the major MMP family such as MMP-3, MMP-9, MMP-11 and MT1-MMP at the mRNA in 44 esophageal squamous cell carcinoma (ESCC) that were previously characterized for MMP-7, MMP-1 and MMP-2, and their relation to urokinase system (uPA and uPAR). MT1-MMP, MMP-11 and MMP-2 expressions are closely associated with each other, while MMP-9 and uPAR expressions are inversely associated with the former group. There is no MMP related to clinicopathological factors; however, patients with high MT1-MMP could show worse prognosis, as compared to those with low MT1-MMP expression (p=0.01), as well as MMP-11 did (p=0.02). Both MMP showed clear expression of carcinoma cells by immunohistochemistry. In patients with high MT1-MMP, recurrence was more prominent (23/26: 88.5%) than those with low MT1-MMP (7/18: 38.9%) (p=0.0016). In the 20 cases who died within 3 years, all 15 cases with high MT1-MMP showed initial recurrence of distant metastasis, and the other 5 cases with low MT1-MMP showed locoregional recurrence (p=0.000064). These results could indicate that there is a relevant mechanism of associated expression of clinically significant MMP and that among them, MT1-MMP plays the most critical role in ESCC progression.

Adult↗